Abstracts (first author)

Talk 

Identification of a major natural polymorphism responsible for the sensitivity to the Orsay Virus in Caenorhabditis elegans

Author(s): Bélicard T, Ashe A, Le Pen J, Frézal L, Sarkies P, Lehrbach NJ, Miska EA, Félix M

Summary:

The nematode Caenorhabditis elegans and its natural pathogen, the positive-strand RNA virus Orsay have recently emerged as a new animal model of host-virus interaction. When infected, sensitive strains of C. elegans show disorganization of intestinal cells. The virus was originally detected in the C. elegans isolate JU1580 and is horizontally transmitted. Using a genome-wide association study on 97 wild C. elegans isolates and finer mapping with Near Isogenic Lines, we identified a region of 155 kb in the center of chromosome IV as carrying the major determinant of viral sensitivity. In JU1580, this region contains a 159 base-pair deletion called niDf250, affecting the conserved drh-1 gene (encoding a RIG-I-like helicase). We found that DRH-1 is required for the initiation of an antiviral RNAi pathway and the generation of virus-derived siRNAs (viRNAs). In mammals, RIG-I-domain-containing proteins trigger an interferon-based innate immunity pathway in response to RNA virus infection. Our work in C. elegans demonstrates that the RIG-I domain has an ancient role in viral recognition. We propose that RIG-I acts as modular viral recognition factor that can couple viral recognition to different effector pathways including RNAi and interferon responses. Surprisingly, the drh-1 deletion - the derived sensitive allele - is commonly found in C. elegans wild populations (23% of wild isolates). Two main hypotheses could explain this distribution: 1) niDf250 is linked to a beneficial allele or 2) niDf250 is beneficial by itself in certain conditions. Supporting the first hypothesis, niDf250 lies in a region with strong linkage disequilibrium. To further test these hypotheses, we are now performing laboratory fitness and competition experiments to decipher the impact of the niDf250 allele and the linked region on C. elegans fitness.


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Chairman: Octávio S. Paulo
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Address

XIV Congress of the European Society for Evolutionary Biology

Organization Team
Department of Animal Biology (DBA)
Faculty of Sciences of the University of Lisbon
P-1749-016 Lisbon
Portugal

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